Data, Reagents, Assays and Merits of Proteomics for SARS-CoV-2 Research and Testing

Mol Cell Proteomics. 2020 Sep;19(9):1503-1522. doi: 10.1074/mcp.RA120.002164. Epub 2020 Jun 26.


As the COVID-19 pandemic continues to spread, thousands of scientists around the globe have changed research direction to understand better how the virus works and to find out how it may be tackled. The number of manuscripts on preprint servers is soaring and peer-reviewed publications using MS-based proteomics are beginning to emerge. To facilitate proteomic research on SARS-CoV-2, the virus that causes COVID-19, this report presents deep-scale proteomes (10,000 proteins; >130,000 peptides) of common cell line models, notably Vero E6, Calu-3, Caco-2, and ACE2-A549 that characterize their protein expression profiles including viral entry factors such as ACE2 or TMPRSS2. Using the 9 kDa protein SRP9 and the breast cancer oncogene BRCA1 as examples, we show how the proteome expression data can be used to refine the annotation of protein-coding regions of the African green monkey and the Vero cell line genomes. Monitoring changes of the proteome on viral infection revealed widespread expression changes including transcriptional regulators, protease inhibitors, and proteins involved in innate immunity. Based on a library of 98 stable-isotope labeled synthetic peptides representing 11 SARS-CoV-2 proteins, we developed PRM (parallel reaction monitoring) assays for nano-flow and micro-flow LC-MS/MS. We assessed the merits of these PRM assays using supernatants of virus-infected Vero E6 cells and challenged the assays by analyzing two diagnostic cohorts of 24 (+30) SARS-CoV-2 positive and 28 (+9) negative cases. In light of the results obtained and including recent publications or manuscripts on preprint servers, we critically discuss the merits of MS-based proteomics for SARS-CoV-2 research and testing.

Keywords: ACE2; COVID-19; SARS-CoV-2; Vero E6; clinical proteomics; label-free quantification; mass spectrometry; parallel reaction monitoring; stable-isotope labeling; targeted mass spectrometry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Amino Acid Sequence
  • Angiotensin-Converting Enzyme 2
  • Animals
  • BRCA1 Protein / genetics
  • BRCA1 Protein / metabolism
  • Betacoronavirus / genetics*
  • Betacoronavirus / pathogenicity
  • COVID-19
  • Caco-2 Cells
  • Case-Control Studies
  • Chlorocebus aethiops
  • Coronavirus Infections / genetics*
  • Coronavirus Infections / pathology
  • Coronavirus Infections / virology
  • Gene Expression Regulation
  • Gene Ontology
  • Host-Pathogen Interactions / genetics*
  • Humans
  • Indicators and Reagents
  • Molecular Sequence Annotation
  • Open Reading Frames
  • Pandemics
  • Peptidyl-Dipeptidase A / genetics
  • Peptidyl-Dipeptidase A / metabolism
  • Pneumonia, Viral / genetics*
  • Pneumonia, Viral / pathology
  • Pneumonia, Viral / virology
  • Proteomics / instrumentation
  • Proteomics / methods*
  • SARS-CoV-2
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism
  • Signal Recognition Particle / genetics
  • Signal Recognition Particle / metabolism
  • Signal Transduction
  • Vero Cells
  • Viral Proteins / classification
  • Viral Proteins / genetics*
  • Viral Proteins / metabolism
  • Virus Internalization


  • BRCA1 Protein
  • BRCA1 protein, human
  • Indicators and Reagents
  • SRP9 protein, human
  • Signal Recognition Particle
  • Viral Proteins
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • Serine Endopeptidases
  • TMPRSS2 protein, human